rs6095516

Variant names:

• chr20-49429848-C-T
• rs6095516
• NM_004975.4:c.567+52066G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004975.4(KCNB1):​c.567+52066G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,212 control chromosomes in the GnomAD database, including 4,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (4194 hom., cov: 33)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 1 publications found

Genes affected

KCNB1 (HGNC:6231): (potassium voltage-gated channel subfamily B member 1) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]

KCNB1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 26

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000290421 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004975.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB1	NM_004975.4	MANE Select	c.567+52066G>A		intron	N/A	NP_004966.1	Q14721

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB1	ENST00000371741.6	TSL:1 MANE Select	c.567+52066G>A		intron	N/A	ENSP00000360806.3	Q14721
	KCNB1	ENST00000635465.1	TSL:1	c.567+52066G>A		intron	N/A	ENSP00000489193.1	Q14721
	KCNB1	ENST00000635878.1	TSL:5	c.96+52066G>A		intron	N/A	ENSP00000489908.1	A0A1B0GU02

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26963 AN: 152094 Hom.: 4177 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.177 AC: 27011 AN: 152212 Hom.: 4194 Cov.: 33 AF XY: 0.173 AC XY: 12874 AN XY: 74426

African (AFR) AF: 0.424 AC: 17595 AN: 41470

American (AMR) AF: 0.0872 AC: 1334 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.0611 AC: 317 AN: 5192

South Asian (SAS) AF: 0.0927 AC: 447 AN: 4820

European-Finnish (FIN) AF: 0.0726 AC: 771 AN: 10614

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0854 AC: 5807 AN: 68022

Other (OTH) AF: 0.142 AC: 299 AN: 2110

Alfa AF: 0.184 Hom.: 620

Bravo AF: 0.188

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6095516; hg19: chr20-48046385;